(1) Field of the Invention
The present invention relates to wound dressings, and more particularly to multi-layer wound dressings having an element that is bioabsorbable.
(2) Description of the Related Art
The management and treatment of external wounds and of internal traumas that are consequences of surgery are areas of intense research and commercial interest, and areas in which recent improvements have significantly improved the quality of life of patients.
Chronic wounds remain one of the most difficult and costliest chronic conditions to treat. These types of wounds also have an insidious effect on the lives of the people that suffer from them. The most common complaints of homebound patients involve their limited mobility and the feeling of being isolated. See, e.g., Neil, J. A. et al., Ostomy/Wound Management, 46:28-38 (2000). Many of these patients withdraw from life and some feel like they are vegetating. Therefore, in addition to the financial burden placed on such patients and upon the healthcare system, there is also a large psychosocial cost associated with chronic wounds.
The current protocol for treatment of chronic wounds typically involves debridement followed by covering the wound with typical moist dressings such as hydrocolloids, hydrogels, alginates and the like. Some of these types of dressings are described in, for example, U.S. Pat. No. 4,570,629, which describes a hydrogel membrane formed from biodegradable copolyelectrolytes. Other such formulations are described in U.S. Pat. Nos. 4,973,466, 5,604,200, 5,679,371 and 6,039,940. U.S. Pat. No. 5,674,523 combines a hydrogel layer with a vapor permeable bacterial barrier.
The use of collagen in wound dressings has been the focus of much work. Such dressings have been fabricated as compressed foam (U.S. Pat. No. 3,800,792), a two-layer dressing of a crosslinked composite of collagen and mucopolysaccharide covered with a moisture transmission control membrane (U.S. Pat. No. 4,060,081), and a dressing made from collagen in combination with a resorbable biopolymer such as fibrinogen (U.S. Pat. No. 4,407,787). Other collagen-based dressings are described in U.S. Pat. Nos. 4,703,108, 4,759,354, 4,834,734, 4,837,285, 4,841,962, 4,970,298, 5,116,824, 5,536,656, 5,579,570, 5,733,337 and 5,863,984.
In U.S. Pat. No. 4,947,840, the use of collagen, as well as synthetic polymers, such as polylactides or polyglycolic acids, was described for the production of biodegradable templates for regeneration of tissues. Factors such as pore size of the template and pore volume fraction were shown to control the rate of wound contraction—especially for implant-containing wounds. U.S. Pat. No. 5,856,367 describes a method of producing biocompatible, porous matrices containing a bioabsorbable matrix (collagen is used to form the matrix), where a volume orientation aid is employed to obtain pore formation.
Dressings and compositions that provide drug delivery features are described in, for example, U.S. Pat. No. 4,178,361, which describes a sustained release pharmaceutical composition in a hydrogel-forming matrix. U.S. Pat. No. 4,683,142 describes a multilayered sheet material consisting of a glycoprotein matrix containing substances which cause blood coagulation, and U.S. Pat. No. 5,593,395 describes a multi-layer dressing having an adhesive release sheet containing a topical drug or medicine.
The use of bioabsorbable synthetic materials in wound dressings has been reported in several publications, such as the use of fabric or sponge made from polyglycolic acid (U.S. Patent No. 3,875,937), or polyglycolic acid on which a vapor permeable film had been deposited (U.S. Pat. No. 3,903,882). The use of an enzymatically degradable material, poly(N-acetyl-D-glucosamine), as sutures, absorbable fabrics, gauze, bone splints and the like has been described in U.S. Pat. No. 4,074,336. U.S. Pat. No. 5,955,578 describes a matrix containing attachment peptides of less than 30 amino acids, which are conjugated to a biodegradable polymer, such as, for example, hyaluronic acid.
The use of beneficial coatings on dressing materials has also been reported. For example, U.S. Pat. No. 4,265,233 describes a method of fixing blood coagulation factor XIII to a dressing material to aid in wound healing.
More advanced forms of treatment, such as the use of growth factor gels and artificial skin type products recently have been introduced with some degree of success. While some of the products have produced significantly better outcomes than the typical dressings, they can be very costly and still do not cause healing in a significant number of wounds. See, e.g., Reuters Medical News, (Jun. 15, 2000) at www.upmc.com/reuters/prof/2000/06/06. 15/20000615clin004.html, and Brem, H. et al., Arch. Surg. 135:627-634 (2000).
One tissue-engineered product utilizes cells, such as fibroblast cells, that are grown on a bovine collagen scaffold to mimic the dermis of the skin. Keratinocytes are grown on top of the dermal layer to form the epidermal layer. These procedures are carried out in an in vitro environment. The complexity of the production process and the raw materials that are required cause the product to be relatively costly, and because it contains living cells, it requires special packaging and has a relatively limited shelf life. See, e.g., Parenteau, N., Sci. American, 280(4):83-84 (1999). Another living skin replacement is composed of living stromal tissue, such as fibroblasts, cultured upon a three-dimensional framework and a transitional covering. (U.S. Pat. No. 5,460,939). The use of extracellular matrix material deposited by a culture of stromal cells grown on a support matrix is described in U.S. Pat. No. 5,830,708.
Another method of skin regeneration includes covering the wound with a collagen glycosaminoglycan matrix, allowing infiltration of the matrix by mesenchymal cells and blood vessels and applying a cultured epithelial autograft sheet grown from epidermal cells taken from the same patient at a wound-free site on the patient's body surface. (U.S. Pat. No. 5,489,304).
Although treatment methods that provide artificial skin that contains living cells, or is prepared from cell culture, are often effective and remain very promising, their application can also be time-consuming and expensive. Moreover, some of these techniques and products are limited to use only on the patient from which the cells were obtained. Therefore, methods of wound treatment that are relatively inexpensive, easy to apply, and can be applied to any patient quickly after the wound has been incurred, would be useful.
Several new dressings have shown promise in helping to overcome some of these defects. For example, EP 0 099 758 A2 describes a composite, multilayered wound dressing having a semipermeable membrane, a permeable supporting membrane, and a biodegradable tissue interface. A dressing described in EP 0 227 955 A2 is similar. However, in neither patent is there an indication that the biodegradable tissue interface layer serves as a scaffold for cell growth.
Canadian Patent No. 2,109,672 describes a multilayer wound dressing that includes a wound contact layer of biocompatible material, a molecular filtration membrane having a maximum pore size of about 0.5 microns, and an absorbent layer atop the molecular filtration membrane. In use, the membrane retains biopolymers and wound healing factors at the wound surface while excluding bacteria and allowing rapid egress of wound exudate into the absorbent layer. The wound contact layer is typically formed from a bioabsorbable material that forms a bioabsorbable gel upon contact with wound exudate. However, as in the dressings described just above, the wound contact layer of this dressing apparently does not serve as a scaffold for cell growth.
WO 97/46,265 describes a multi-layered wound dressing that includes a fluid permeable and bioresorbable lower section that is adjacent the wound and that promotes healing of the wound. The bioresorbable material can be made from biodegradable esters such as poly(3-hydroxybutyrate). The use of a protein-free bioresorbable polymer is said to be advantageous because it appears to stimulate healing by stimulating macrophages and working as a scaffold for cell growth. The polymer is also said to stimulate vascularization and microcirculation. The dressing includes an upper section that is permeable to vapor and impermeable to bacteria. An intermediate section of, for example, cellulose fibers, polyacrylic acids, or preferably a hydrocolloid, may also be added to serve as an absorbent layer. There is no indication that this section is resistant to adhesion or penetration by growing cells of the healing tissue and it could be expected that the large pores of a cellulose fiber structure might invite such penetration. Therefore, when the dressing is changed after being in place for an extended period, either the intermediate layer must be left in place, or some damage to any cells or tissue that have penetrated the intermediate layer would be expected.
Despite these advances, there is still a need for a dressing that accelerates wound healing, avoids trauma and disturbance of healing due to removal or replacement of the dressing, provides management of wound exudate, can be stored for extended periods of time and is easily used on any patient.
It is to such needs that the present invention is directed.